Our goal is to establish basic science foundations and engineering principles for the broad applications of theranostic (therapeutic+diagnostic) nano-objects, defined as compact autonomous molecular devices capable of analyzing multiple biomarkers before signaling that there are pathological events or before taking corrective actions. Our effort will center on methods to control behavior of dynamic neggs (nano-eggs), made of deoxyribonucleic acids, and comprising sensors, imaging and/or therapeutic moieties, and molecular computing functions. Neggs can open (be unlocked) or close (be locked) on cue, and this cue can be integrated information on the presence or absence of one or more biomarkers. In order to showcase the transformative potential of theranostic nano-objects, we will map increasingly complex engineered behaviors of neggs to proof-of-concepts for therapeutic applications for which no other existing technologies are satisfactory. For example, we will: (i) open a negg if an analyte raises above (e.g., glucose) or drops below (e.g., vasopressin) its normal concentration; (ii) mark for elimination/imaging narrow subpopulations of cells based on multiple surface markers, while protecting cells that differ in a single marker (e.g., on lymphocytes); and (iii) demonstrate amplification of MRI contrast agents on a targeted cell type (exemplified on b-cells). 1 PUBLIC HEALTH RELEVANCE: Theranostic (therapeutic+diagnostic) nano-objects are autonomous nanoscopic devices capable of analyzing in vivo multiple biomarkers before signaling the presence of pathological events (imaging/diagnostics) or before taking corrective actions when needed (therapeutics). They can autonomously control levels of glucose in diabetes, prevent irreversible shock in an intensive care patient, or selectively eliminate very narrow subpopulations of cells in a cancer patient.